Role of organic cation transporters in the renal handling of therapeutic agents and xenobiotics
Section snippets
Molecular Physiology of OCTs
OCT1 was cloned from a rat renal cDNA library (Gründemann et al., 1994) and proved to be the initial member of a large family of transport proteins (the OCT Family, here referred to collectively as the ‘OCTs’). Within the Human Genome Organization (HUGO) Nomenclature Committee Database, the OCTs and their homologues have been organized into the SLC22A Family of solute carriers (Hediger et al., 2004). Additionally, the OCTs are recognized as being members of the Major Facilitator Superfamily of
Molecular determinants of OCT selectivity
It would be of obvious value to be able to predict with reasonable precision the extent to which individual elements of the renal OC secretory process interact with the vast array of physiologically and pharmacologically important Type I OCs. Moreover, a reasonably precise predictive model of substrate–transporter interaction could play a critically important role in the design of new pharmacological agents. The hallmark ‘multispecificity’ of renal OC secretion, as commented on earlier, has
References (83)
- et al.
Structure and mechanism of the lactose permease of Escherichia coli
Science
(2003) - et al.
Mutation of amino acid 475 of rat organic cation transporter 2 (rOCT2) impairs organic cation transport
Biochimie
(2004) - et al.
Mechanism of electrogenic cation transport by the cloned organic cation transporter 2 from rat
J. Biol. Chem.
(2000) - et al.
Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1
J. Biol. Chem.
(1996) - et al.
Molecular identification of a novel carnitine transporter specific to human testis. Insights into the mechanism of carnitine recognition
J. Biol. Chem.
(2002) - et al.
Organic anion and cation transporters occur in pairs of similar and similarly expressed genes
Biochem. Biophys. Res. Commun.
(2003) - et al.
Evidence for an organic cation-proton antiport system in brush-border membranes isolated from the human term placenta
J. Biol. Chem.
(1988) - et al.
Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta
J. Biol. Chem.
(1998) - et al.
Carnitine transport by organic cation transporters and systemic carnitine deficiency
Mol. Genet. Metab.
(2001) - et al.
A missense mutation of mouse OCTN2, a sodium-dependent carnitine cotransporter, in the juvenile visceral steatosis mouse
Biochem. Biophys. Res. Commun.
(1998)
Membrane localization of the electrogenic cation transporter rOCT1 in rat liver
Biochem. Biophys. Res. Commun.
Axial heterogeneity of organic cation transport along the rabbit renal proximal tubule: studies with brush-border membrane vesicles
Biochim. Biophys. Acta
Renal secretion of organic anions and cations
Kidney Int.
Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions
Biochem. Biophys. Res. Commun.
Molecular cloning and characterization of two novel transport proteins from rat kidney
FEBS Lett.
Molecular and functional characterization of organic cation/carnitine transporter family in mice
J. Biol. Chem.
Na(+)-coupled transport of L-carnitine via high-affinity carnitine transporter OCTN2 and its subcellular localization in kidney
Biochim. Biophys. Acta
Specificity of transporters for ‘organic anions’ and ‘organic cations’ in the kidney
Biochim. Biophys. Acta
cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family
Biochem. Biophys. Res. Commun.
Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta
Biochim. Biophys. Acta
Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1
Am. J. Physiol.: Renal, Physiol.
Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1
Mol. Pharmacol.
Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans
Eur. J. Clin. Pharmacol.
The Molecular Physiology of Renal Organic Cation Transport
Structure of renal organic anion and cation transporters
Am. J. Physiol.: Renal, Physiol.
Utility of Mdr1-gene deficient mice in assessing the impact of P-glycoprotein on pharmacokinetics and pharmacodynamics in drug discovery and development
Curr. Drug Metab.
Renal tubular transport of organic anions and cations
Basolateral tetraethylammonium transport in intact tubules: specificity and trans-stimulation
Am. J. Physiol.
The molecular pharmacology of organic anion transporters: from DNA to FDA?
Mol. Pharmacol.
Novel slc22 transporter homologs in fly, worm, and human clarify the phylogeny of organic anion and cation transporters
Physiol. Genomics
Arginine 454 and lysine 370 are essential for the anion specificity of the organic anion transporter, rOAT3
Biochemistry
Role of aromatic transmembrane residues of the organic anion transporter, rOAT3, in substrate recognition
Biochemistry
The role of the V-ATPase in renal epithelial H+ transport
J. Exp. Biol.
The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules
J. Pharmacol. Exp. Ther.
Selectivity of the polyspecific cation transporter rOCT1 is changed by mutation of aspartate 475 to glutamate
Mol. Pharmacol.
Drug excretion mediated by a new prototype of polyspecific transporter
Nature
The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins. Introduction
Pfluegers Arch.
Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli
Science
Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations
Mol. Cell. Biol.
Functional mapping of rbOCT1 and rbOCT2 activity in the S2 segment of rabbit proximal tubule
Am. J. Physiol.: Renal, Physiol.
Cited by (112)
ADME/T-based strategies for paraquat detoxification: Transporters and enzymes
2021, Environmental PollutionMechanisms and genetics of drug transport
2021, Atkinson's Principles of Clinical PharmacologyUptake Transporters
2018, Comprehensive Toxicology: Third EditionInteraction of pharmaceutical excipients with organic cation transporters
2017, International Journal of PharmaceuticsCitation Excerpt :OCTs transport many drugs such as beta-blockers, quinidine, cisplatin, morphine, metformin, phenoxybenzamine, prazosin, procainamide, and cimetidine (Ciarimboli et al., 2005; Kimura et al., 2005; Koepsell et al., 2007). Thus, the renal OCTs are important determinant of drug efficacy and toxicity (Ciarimboli et al., 2005; Wright 2005; Choi and Song, 2008). It has been reported that metformin fails to reduce fasting plasma glucose in type 2 diabetes patients who have mutation of OCT1 which is explained by decreasing hepatic uptake of metformin (Shu et al., 2007).
Nanotechnologies for the treatment of colon cancer: From old drugs to new hope
2016, International Journal of PharmaceuticsWhy Does the Intestine Lack Basolateral Efflux Transporters for Cationic Compounds? A Provocative Hypothesis
2016, Journal of Pharmaceutical Sciences